NSIDRC Journal Article Alert — May 8, 2009

Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.

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Sudden Infant Death

1. Highet AR, Berry AM, Goldwater PN

Novel hypothesis for unexplained Sudden Unexpected Death in Infancy (SUDI)

Arch Dis Child. 2009 May 3. [Epub ahead of print]

University of Adelaide, Australia.

OBJECTIVE: Two recent retrospective studies independently reported typically pathogenic bacteria in normally sterile sites of infants succumbing to Sudden Unexpected Death in Infancy (SUDI). These findings suggested a proportion of unexplained SUDI might be triggered by bacteraemia. The objective was to assess these observations in the context of the pathology and epidemiology of SIDS in relation to the role of infection and inflammation as triggers of these deaths. DESIGN: A review of the literature to identify potential risk factors for unexplained infant deaths and proposal of a theoretical model for SUDI. RESULTS: Pathologic and epidemiological evidence suggests a hypothesis based on three factors: bacterial translocation; pathogen pattern recognition insufficiency; prenatal exposure to infection. CONCLUSION: We propose that sterile site infections in which common toxigenic bacteria are identified indicate a brief bacteraemic episode prior to death. This might reflect an ineffective innate response to invasive pathogens that result in reduced clearance of the bacteria. Thymomegaly observed consistently among infants diagnosed under the category of Sudden Infant Death Syndrome might have its origins in prenatal life, perhaps generated via in utero infection or exposure to microbial antigens which results in thymocyte priming. There is consistent evidence for an infectious aetiology in many unexplained SUDI. Future directions for research are suggested.

2. Richardson HL, Walker AM, Horne RS

Maternal smoking impairs arousal patterns in sleeping infants

Sleep. 2009 Apr 1;32(4):515-21

Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.

OBJECTIVE: Impairment of the arousal process from sleep is thought to be involved in the pathogenesis of sudden infant death syndrome (SIDS). We hypothesized that a greater propensity for cortical arousal in the prone position may, in a normal infant, be a protective mechanism to promote complete arousal in a vulnerable sleeping position, a protection that is absent in SIDS victims. We aimed to examine the arousal process in a group of infants exposed to maternal smoking, who are thus at higher risk for SIDS. DESIGN: Twelve healthy, full-term infants born to smoking mothers were studied using daytime polysomnography at 2 to 4 weeks, 2 to 3 months and 5 to 6 months postnatal age. Data were compared with 13 healthy infants born to nonsmoking mothers. Arousal was induced by pulsatile air-jet stimulation to the nostrils during active and quiet sleep, in both supine and prone positions. For each stimulus, physiologic and electroencephalogram changes were visually assessed and arousal responses were classified as sub-cortical activation or cortical arousal. RESULTS: In smoke-exposed infants, the progression from sub-cortical activation to cortical arousal was depressed at 2 to 4 weeks and 5 to 6 months. There was no effect of maternal smoking observed at 2 to 3 months; however, a significant dose-dependent relationship between cortical activation proportions and urinary cotinine levels was present in both supine and prone positions. CONCLUSION: We have shown that maternal smoking is associated with impaired arousal processes to trigeminal stimulation that may increase the risk for SIDS. This further highlights the importance of public education of the risks of maternal smoking.

3. Niklasson B, Almqvist PR, Hörnfeldt B, Klitz W

Sudden infant death syndrome and Ljungan virus

Forensic Sci Med Pathol. 2009 May 1. [Epub ahead of print]

Apodemus AB, Grevgatan 38, SE-114 53, Stockholm, Sweden, Bo.Niklasson@Apodemus.se.

Ljungan virus (LV) has recently been associated with perinatal death in its natural rodent reservoir and also with developmental disorders of reproduction in laboratory mice. A strong epidemiological association has been found between small rodent abundance in Sweden and the incidence of intrauterine fetal death (IUFD) in humans. LV antigen has been detected in half of the IUFD cases tested. The question was therefore raised whether sudden infant death syndrome (SIDS) might be associated with rodent abundance, and whether the virus is present in cases of SIDS. Variation in the incidence of SIDS using the Swedish cause-of-death database tracked the changes in the population fluctuations of native rodents. Formalin-fixed tissues from the brain, heart, and lung were investigated from cases of SIDS, SIDS with lymphocytic infiltration of the myocardium (myocarditis) and myocarditis cases using LV specific immunohistochemistry (IHC). Ljungan virus was detected in the brain, heart, and lung tissue from all three of the patient categories investigated using IHC. These studies suggest that LV may play a prominent role in infant death, and that IUFD and SIDS may have common etiological underpinnings.

4. Sexton S, Natale R

Risks and benefits of pacifiers

Am Fam Physician. 2009 Apr 15;79(8):681-5

Georgetown University School of Medicine, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. makkars@georgetown.edu

Physicians are often asked for guidance about pacifier use in children, especially regarding the benefits and risks, and when to appropriately wean a child. The benefits of pacifier use include analgesic effects, shorter hospital stays for preterm infants, and a reduction in the risk of sudden infant death syndrome. Pacifiers have been studied and recommended for pain relief in newborns and infants undergoing common, minor procedures in the emergency department (e.g., heel sticks, immunizations, venipuncture). The American Academy of Pediatrics recommends that parents consider offering pacifiers to infants one month and older at the onset of sleep to reduce the risk of sudden infant death syndrome. Potential complications of pacifier use, particularly with prolonged use, include a negative effect on breastfeeding, dental malocclusion, and otitis media. Adverse dental effects can be evident after two years of age, but mainly after four years. The American Academy of Family Physicians recommends that mothers be educated about pacifier use in the immediate postpartum period to avoid difficulties with breastfeeding. The American Academy of Pediatrics and the American Academy of Family Physicians recommend weaning children from pacifiers in the second six months of life to prevent otitis media. Pacifier use should not be actively discouraged and may be especially beneficial in the first six months of life.

5. Kinney HC, Richerson GB, Dymecki SM, Darnall RA, Nattie EE

Annu Rev Pathol. 2009;4:517-50

The brainstem and serotonin in the sudden infant death syndrome

Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. Hannah.Kinney@childrens.harvard.edu

The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death.

Miscarriage/Stillbirth/Prenatal Issues

1. Culic V, Konjevoda P, Mise K, Kardum G, Matijevic T, Pavelic J

Genitourinary diseases prior spontaneous abortion as a risk factor for recurrent pregnancy loss

Coll Antropol. 2009 Mar;33(1):187-92

Department for Medical Genetics, Laboratory for Human Genetics, University Hospital Center "Split", Split, Croatia.

The etiology of recurrent spontaneous abortion (RSA) is still unexplained. Many couples do not find the cause of their RSA at all. The purpose of this research was to evaluate the association between recurrent pregnancy loss and previous (cured prior to pregnancy) acute/chronic genitourinary infections in both parents. Couples (226) having two or more (up to six) spontaneous abortions were analyzed in this retrospective case-control study. The control group consisted of 124 couples with neither miscarriages nor complicated pregnancies in their past. The data (serum immunological markers, karyotype, flow cytometry data, PHD) were collected from their medical charts. It was found that there was no statistically significant difference in average weeks of pregnancy in which the second, third and fourth abortion occurred. There was a statistically significant difference in previously experienced genitourinary infections between women from the RSA group and the control group, as well as for men from the RSA group and the control group. It can be concluded that past infections of the maternal and/or paternal genitourinary system may be the causal factor for recurrent pregnancy loss and can also pre-determine women that are of greater susceptibility to preterm pregnancy. Therefore the genetic counseling of couples should include thorough medical and family history of both partners and their first- and second-degree relatives in conjunction with typical medical examination.

2. Wilkowska-Trojniel M, Zdrodowska-Stefanow B, Ostaszewska-Puchalska I, Red?ko S, Przepie?? J, Zdrodowski M

Adv Med Sci. 2009 Apr 28:1-5. [Epub ahead of print]

The influence of Chlamydia trachomatis infection on spontaneous abortions

Centre for STD Research and Diagnostics, Bialystok, Poland.

Purpose: The aim of the study was to evaluate the frequency of Chlamydia trachomatis (C.t.) infection among women who experienced a miscarriage.Materials and Methods: Patients referred to the Centre for STD Research and Diagnostics in Bialystok from the Department of Perinatology and from gynaecological outpatient clinics, after spontaneous abortion were enrolled in the study. C.t. infection diagnostics were performed among 76 women with 1 miscarriage and 44 patients with >/=2 miscarriages in anamnesis. Forty-six patients in the 2nd and the 3rd trimester of normal pregnancy served as a comparative group. Endocervical swabs as well as blood serum were obtained. To detect chlamydial DNA, direct PCR method was performed (Roche, Molecular Systems, N.J., USA). To detect IgA and IgG specific anti-chlamydial antibodies we used immunoenzymatic assay (medac, Hamburg, Germany).Results: In patients with 1 miscarriage (gr. 1), C.t. infection by means of PCR was detected in 11.8% of women (p=0.029), in patients with >/=2 miscarriages (gr. 2) in 9.1% (p=0.198) and in the comparative group (gr. 0) in 2.2%. Specific anti-chlamydial antibodies IgA class were detected in: 7.9 (p=0.082) in group 1, 4.5% (p=0.236) in group 2 and in 0% in group 0, and IgG class in 21.1% (p=0.024), 36.4% (p=0.000) and in 4.4%, respectively.Conclusions: 1. C.t. infection is an important causative agent of miscarriages in women. 2. C.t. infection diagnostic procedures should be considered in screening tests during pregnancy.

3. De la Fuente-Cortés BE, Cerda-Flores RM, Dávila-Rodríguez MI, García-Vielma C, De la Rosa Alvarado RM, Cortés-Gutiérrez EI

Chromosomal abnormalities and polymorphic variants in couples with repeated miscarriage in Mexico

Reprod Biomed Online. 2009 Apr;18(4):543-8

Departamento de Genética, Facultad de Medicina, Universidad Autónoma de Nuevo León, México. elvacortes@cibinmty.net

Cytogenetic studies have an important role in the evaluation of couples with repeated miscarriages and poor obstetric history. To estimate the prevalence of chromosomal abnormalities and polymorphic variants in 158 couples with repeated miscarriages, a cross-sectional study was conducted in Monterrey, Mexico from 1995 to 2003. Peripheral blood lymphocytes were cultured for chromosomal studies using standard methods. Twelve couples showed chromosomal abnormalities (7.60%), two Robertsonian translocations (1.27%), two balanced translocations (1.27%), one inversion (0.63%), and one a novel insertion (0.63%). This insertion [46, XX, ins (15;8) (q26;p11p23)] is unique, and is the third reported in association with repeated abortion. Mosaicism was observed in six couples (3.80%, three with structural abnormalities and three with numerical abnormalities). A female to male ratio of 1.4:1 was observed. In addition to these chromosomal abnormalities, polymorphic variants in constitutive heterochromatin of the 1qh+, 9qh+, and 16qh+ chromosomes were observed in 25 couples (15.82%), of the Yqh+ chromosome in 21 couples (13.29%), and of satellite in 35 couples (22.15%). In conclusion, chromosome analysis is necessary for appropriate clinical management of these patients.

4. Choe JK, Check JH, Chern R

Septoplasty allows successful delivery in a primary aborter with six previous first trimester miscarriages

Clin Exp Obstet Gynecol. 2009;36(1):15-6

The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, Camden, NJ, USA.

PURPOSE: To demonstrate that septoplasty can correct a problem of recurrent miscarriage. METHODS: The patient was a primary aborter with a history of six consecutive miscarriages. Septoplasty by hysteroscopy/laparoscopy was performed. The septum was diagnosed by 3D sonohysterography. RESULTS: She delivered a healthy live baby at 36 weeks. CONCLUSION: This case clearly demonstrates that sometimes the uterine septum plays an important role in recurrent miscarriage and that septoplasty can improve the chances of successful delivery. The case also shows that a definitive diagnosis of a bicornuate uterus by HSG and/or MRI can not be made.

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